Explore TMB and number of mutations across multiple timepoints of the PBTA Cohort

Tumor evolution project

Data used

In this notebook, we are using the tmb_genomic.tsv file generated from the 01-preprocess-data.Rmd script.

Set up

Directories and File Inputs/Outputs

Read in data and process

Error in `select()`:
! Can't subset columns that don't exist.
✖ Column `patient_id` doesn't exist.
Backtrace:
 1. ... %>% ...
 3. dplyr:::select.data.frame(...)

TMB per Patient case

We will explore TMB per Kids_First_Participant_ID over time by creating stacked barplots.

[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/TMB-genomic-total.pdf\

png 
  2 

Attention: Hypermutant TMB defined as ≥10 Mb, and Ultrahypermutant TMB defined as ≥100 mutations/Mb in pediatric brain tumors (https://pubmed.ncbi.nlm.nih.gov/29056344/).

Here, we notice that there are samples with high TMB (hyper-mutant samples). Next, we will exclude these samples (threshold >= 10) from downstream analysis. Attention is needed in cases with high number of mutations in only one timepoint as this will lead to un-matched longitudinal samples. We will also remove those so we always have matched longitudinal samples.

[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/TMB-genomic-no-hypermutants.pdf\

png 
  2 

TMB across timepoints and cancer types per Patient case

We will explore TMB per cancer group over time by creating dumbbell plots. We classified by using cancer types with the highest number of samples (High- and Low-grade gliomas) versus any other cancer groups.

[1] \High-grade glioma\  \Low-grade glioma\   \Other cancer group\
[1] 1
[1] \High-grade glioma\
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/High-grade glioma-TMB-dumbbell.pdf\

[1] 2
[1] \Low-grade glioma\
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/Low-grade glioma-TMB-dumbbell.pdf\

[1] 3
[1] \Other cancer group\
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/Other cancer group-TMB-dumbbell.pdf\

Total number of mutations across timepoints and cancer types per Patient case

[1] 1
[1] \High-grade glioma\
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/High-grade glioma-Mutations-dumbbell.pdf\

[1] 2
[1] \Low-grade glioma\
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/Low-grade glioma-Mutations-dumbbell.pdf\

[1] 3
[1] \Other cancer group\
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/Other cancer group-Mutations-dumbbell.pdf\

Let’s see if the issue with missing values per sample int he dumbbell plots is bypassed when using jitter plot.

[1] \High-grade glioma\  \Low-grade glioma\   \Other cancer group\
[1] 1
[1] \High-grade glioma\
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/High-grade glioma-TMB-jitter.pdf\

[1] 2
[1] \Low-grade glioma\
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/Low-grade glioma-TMB-jitter.pdf\

[1] 3
[1] \Other cancer group\
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/Other cancer group-TMB-jitter.pdf\

It is not… i have tried with side-by-side barplots and it was the same issue. Dumbbell plots might be more informative to show changes across timepoints. We could consider to use them in later analyses.

Total number of mutations across timepoints and biospecimen sample per Patient case

Here, we want to explore the number of mutations per timepoint and biospecimen sample per patient case.

First, let’s try to use facet_wrap function. Again, we are missing values in timepoints.

[1] 1
[1] \High-grade glioma\
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/High-grade glioma-Mutations-barplot.pdf\

[1] 2
[1] \Low-grade glioma\
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/Low-grade glioma-Mutations-barplot.pdf\

[1] 3
[1] \Other cancer group\
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/Other cancer group-Mutations-barplot.pdf\

But this doesn’t happen when plotting separate barplots per Kids_First_Participant_ID.

 [1] \PT_02J5CWN5\ \PT_0DWRY9ZX\ \PT_1ZAWNGWT\ \PT_2FVTD0WR\ \PT_2MZPGZN1\
 [6] \PT_2YT37G8P\ \PT_37B5JRP1\ \PT_39H4JN6H\ \PT_3GYW6P6P\ \PT_3P3HARZ2\
[11] \PT_3R0P995B\ \PT_3T3VGWC6\ \PT_3VCS1PPF\ \PT_5NS35B66\ \PT_5ZPPR06P\
[16] \PT_62G82T6Q\ \PT_82MX6J77\ \PT_89XRZBSG\ \PT_962TCBVR\ \PT_98QMQZY7\
[21] \PT_99S5BPE3\ \PT_B5DQ8FF0\ \PT_BRVGRXQY\ \PT_BZCJMEX8\ \PT_CWXSP19D\
[26] \PT_CXT81GRM\ \PT_DFQAH7RS\ \PT_DNAJYFZT\ \PT_DVXE38EX\ \PT_FN4GEEFR\
[31] \PT_HE8FBFNA\ \PT_HHG37M6W\ \PT_JNEV57VK\ \PT_JSFBMK5V\ \PT_KMHGNCNR\
[36] \PT_P571HTNK\ \PT_PF04R0BH\ \PT_PR4YBBH3\ \PT_QH9H491G\ \PT_S2SQJVGK\
[41] \PT_T4VN7ZRB\ \PT_TKWTTRQ7\ \PT_TP6GS00H\ \PT_TRZ1N1HQ\ \PT_VTG1S395\
[46] \PT_XA98HG1C\ \PT_XHYBZKCX\ \PT_YK7AD0KK\ \PT_Z4GS3ZQQ\ \PT_ZMKMKCFQ\
[1] 1
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_02J5CWN5-Mutations-barplot.pdf\

[1] 2
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_0DWRY9ZX-Mutations-barplot.pdf\

[1] 3
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_1ZAWNGWT-Mutations-barplot.pdf\

[1] 4
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_2FVTD0WR-Mutations-barplot.pdf\

[1] 5
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_2MZPGZN1-Mutations-barplot.pdf\

[1] 6
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_2YT37G8P-Mutations-barplot.pdf\

[1] 7
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_37B5JRP1-Mutations-barplot.pdf\

[1] 8
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_39H4JN6H-Mutations-barplot.pdf\

[1] 9
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_3GYW6P6P-Mutations-barplot.pdf\

[1] 10
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_3P3HARZ2-Mutations-barplot.pdf\

[1] 11
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_3R0P995B-Mutations-barplot.pdf\

[1] 12
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_3T3VGWC6-Mutations-barplot.pdf\

[1] 13
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_3VCS1PPF-Mutations-barplot.pdf\

[1] 14
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_5NS35B66-Mutations-barplot.pdf\

[1] 15
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_5ZPPR06P-Mutations-barplot.pdf\

[1] 16
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_62G82T6Q-Mutations-barplot.pdf\

[1] 17
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_82MX6J77-Mutations-barplot.pdf\

[1] 18
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_89XRZBSG-Mutations-barplot.pdf\

[1] 19
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_962TCBVR-Mutations-barplot.pdf\

[1] 20
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_98QMQZY7-Mutations-barplot.pdf\

[1] 21
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_99S5BPE3-Mutations-barplot.pdf\

[1] 22
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_B5DQ8FF0-Mutations-barplot.pdf\

[1] 23
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_BRVGRXQY-Mutations-barplot.pdf\

[1] 24
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_BZCJMEX8-Mutations-barplot.pdf\

[1] 25
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_CWXSP19D-Mutations-barplot.pdf\

[1] 26
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_CXT81GRM-Mutations-barplot.pdf\

[1] 27
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_DFQAH7RS-Mutations-barplot.pdf\

[1] 28
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_DNAJYFZT-Mutations-barplot.pdf\

[1] 29
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_DVXE38EX-Mutations-barplot.pdf\

[1] 30
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_FN4GEEFR-Mutations-barplot.pdf\

[1] 31
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_HE8FBFNA-Mutations-barplot.pdf\

[1] 32
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_HHG37M6W-Mutations-barplot.pdf\

[1] 33
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_JNEV57VK-Mutations-barplot.pdf\

[1] 34
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_JSFBMK5V-Mutations-barplot.pdf\

[1] 35
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_KMHGNCNR-Mutations-barplot.pdf\

[1] 36
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_P571HTNK-Mutations-barplot.pdf\

[1] 37
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_PF04R0BH-Mutations-barplot.pdf\

[1] 38
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_PR4YBBH3-Mutations-barplot.pdf\

[1] 39
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_QH9H491G-Mutations-barplot.pdf\

[1] 40
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_S2SQJVGK-Mutations-barplot.pdf\

[1] 41
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_T4VN7ZRB-Mutations-barplot.pdf\

[1] 42
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_TKWTTRQ7-Mutations-barplot.pdf\

[1] 43
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_TP6GS00H-Mutations-barplot.pdf\

[1] 44
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_TRZ1N1HQ-Mutations-barplot.pdf\

[1] 45
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_VTG1S395-Mutations-barplot.pdf\

[1] 46
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_XA98HG1C-Mutations-barplot.pdf\

[1] 47
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_XHYBZKCX-Mutations-barplot.pdf\

[1] 48
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_YK7AD0KK-Mutations-barplot.pdf\

[1] 49
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_Z4GS3ZQQ-Mutations-barplot.pdf\

[1] 50
[1] \/home/rstudio/pbta-tumor-evolution/analyses/tmb-vaf-longitudinal/plots/PT_ZMKMKCFQ-Mutations-barplot.pdf\

sessionInfo()

R version 4.2.3 (2023-03-15)
Platform: x86_64-pc-linux-gnu (64-bit)
Running under: Ubuntu 22.04.2 LTS

Matrix products: default
BLAS:   /usr/lib/x86_64-linux-gnu/openblas-pthread/libblas.so.3
LAPACK: /usr/lib/x86_64-linux-gnu/openblas-pthread/libopenblasp-r0.3.20.so

locale:
 [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
 [3] LC_TIME=en_US.UTF-8        LC_COLLATE=en_US.UTF-8    
 [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
 [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
 [9] LC_ADDRESS=C               LC_TELEPHONE=C            
[11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       

attached base packages:
[1] grid      stats     graphics  grDevices utils     datasets  methods  
[8] base     

other attached packages:
 [1] ggthemes_4.2.4  lubridate_1.9.2 forcats_1.0.0   stringr_1.5.0  
 [5] dplyr_1.1.1     purrr_1.0.1     readr_2.1.4     tidyr_1.3.0    
 [9] tibble_3.2.1    ggplot2_3.4.0   tidyverse_2.0.0

loaded via a namespace (and not attached):
 [1] highr_0.10       bslib_0.4.2      compiler_4.2.3   pillar_1.9.0    
 [5] jquerylib_0.1.4  tools_4.2.3      bit_4.0.5        digest_0.6.31   
 [9] timechange_0.2.0 jsonlite_1.8.4   evaluate_0.20    lifecycle_1.0.3 
[13] gtable_0.3.3     pkgconfig_2.0.3  rlang_1.1.0      cli_3.6.1       
[17] parallel_4.2.3   yaml_2.3.7       xfun_0.38        fastmap_1.1.1   
[21] withr_2.5.0      knitr_1.42       generics_0.1.3   vctrs_0.6.2     
[25] sass_0.4.5       hms_1.1.3        bit64_4.0.5      rprojroot_2.0.3 
[29] tidyselect_1.2.0 glue_1.6.2       R6_2.5.1         fansi_1.0.4     
[33] vroom_1.6.1      rmarkdown_2.21   farver_2.1.1     tzdb_0.3.0      
[37] magrittr_2.0.3   scales_1.2.1     htmltools_0.5.5  colorspace_2.1-0
[41] labeling_0.4.2   utf8_1.2.3       stringi_1.7.12   munsell_0.5.0   
[45] cachem_1.0.7     crayon_1.5.2